Long-term administration of prazosin improves bladder storage function: results from a study in spontaneously hypertensive rats

Int J Urol. 2011 Nov;18(11):785-91. doi: 10.1111/j.1442-2042.2011.02849.x. Epub 2011 Sep 8.

Abstract

Objectives: To investigate the effects of long-term administration of the α(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT).

Methods: Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry.

Results: The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle.

Conclusions: Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology*
  • Animals
  • Female
  • Immunohistochemistry
  • Lumbar Vertebrae
  • Neurons, Afferent / drug effects
  • Prazosin / pharmacology*
  • Proto-Oncogene Proteins c-fos / analysis
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Spinal Cord / chemistry*
  • Spinal Cord / pathology
  • Time Factors
  • Urinary Bladder / physiology*
  • Urination / drug effects
  • Urodynamics / drug effects*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Proto-Oncogene Proteins c-fos
  • Prazosin